Vanadyl ions stimulate K+ uptake into isolated perfused rat liver via the Na+/K+-pump by a tyrosine kinase-dependent mechanism.
Vanadium salts mimic most metabolic effects of insulin in vitro. We report here that vanadyl sulfate (VOSO4) and sodium vanadate (NaVO3) stimulate net K+ uptake in isolated perfused rat liver. Stimulation was evident at low concentrations of vanadyl ions (range 1-20 microM) and occurred within minutes following the addition of VOSO4. By comparison with VOSO4, insulin had less of a stimulatory effect on K+ uptake. Ouabain prevented the activating effect of VOSO4 on K+ uptake. Following a VOSO4 challenge, measured intracellular Na+ concentration ([Na+]i) fell (control, 17.1 +/- 1.2; VOSO4-treated, 13.0 +/- 1.1 mmol.g-1 wet weight, P = 0.027). The results indicate that active K+ uptake via the Na+/K+-ATPase was stimulated by vanadyl ions. An indirect mechanism due to changes in [Na+]i can be excluded. The tyrosine kinase inhibitor genistein was found to inhibit stimulation of K+ by vanadyl and vanadate ions which are known inhibitors of phosphotyrosine phosphatases. We conclude that stimulation of active K+ influx involves a tyrosine kinase. Possible mechanisms include phosphorylation at tyrosine residues and direct activation of the Na+/K+-ATPase, or phosphorylation of other proteins that regulate the activity or number of pumps in the cells.
Bruck
R
R
The Department of Gastroenterology, The E. Wolfson Medical Center, Holon, Sackler School of Medicine,
Halpern
Z
Z
Aeed
H
H
Shechter
Y
Y
Karlish
S J
SJ
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013268:Stimulation, Chemical; D014638:Vanadates / Q000494:pharmacology*; D017968:Vanadium Compounds / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007328:Insulin; D017968:Vanadium Compounds; D014638:Vanadates; D010042:Ouabain; C034028:vanadyl sulfate; D011505:Protein-Tyrosine Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium